10.1002/asia.201800652
Chemistry - An Asian Journal
COMMUNICATION
[2+2]-cycloaddition with dimethylketene under irradiation with
light generated the corresponding cycloadduct 10 in good yield
with high enantioselectivity (Scheme 2C).
Conflict of interest
The authors declare no conflict of interest.
Keywords: alkylation • phase-transfer catalyst • N-
arylhydrazone • α-keto ester • isatin
[1]
For recent reviews on reactions that involve N-substituted hydrazones
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[2]
Scheme 2. Subsequent Transformations of Alkylation Products 2.
In conclusion, we have developed an enantioselective alkylation
of N-arylhydrazones derived from α-keto esters and isatin
derivatives, which serve as α-azo carbanion equivalents under
asymmetric phase-transfer conditions. The resulting azo
compounds, which contain a tetra-substituted stereogenic center,
were obtained in good yields with high chemo- and
enantioselectivity, and can be readily converted into chiral amino
esters, hydrazine derivatives, and aza-β-lactams under retention
of the enantiopurity.
[3]
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Experimental Section
[5]
[6]
On the influence of the stoichiometry of bases and alkyl halides, see
Table S1 in Supporting Information.
General Procedure for the Enantioselective Alkylation of N-
Arylhydrazones: A Schlenk tube was charged with the N-arylhydrazone
(0.1 mmol), phase-transfer catalyst (0.005 mmol) and base (0.5 mmol),
before the mixture was placed under an atmosphere of argon. Then,
toluene (1 mL) and alkyl halide (0.5 mmol) were added. The reaction was
stirred at room temperature for 16-96 h. After the consumption of the
starting materials, the mixture was passed through a short column on
silica gel in order to remove the remaining base and all salts that formed
during the reaction. The filtrate was concentrated and the residue was
purified by preparative layer chromatography (hexane/ethyl acetate as
eluent) to afford the targeted products.
In the presence of chiral phase-transfer catalysts, (R)-5a and (R,R)-5c,
the enantioselective alkylation of tert-butyl alaninate-aromatic aldehyde
Schiff base gave rise to the (S)-isomer of dialkylamino acid via the
intermediary (E)-enolate by the π−π interaction between Ar and
binaphthyl moieties (T. Ooi, M. Kameda, K. Maruoka, J. Am. Chem.
Soc., 121, 6519-6520 (1999)). In the case of substrate (E)-1c, we also
obtained the (S)-isomer of product 2c~m via a similar (E)-enolate.
Hence, we think about similar transition state structures, although we
do not have the solid evidence on such a transition state structure from
the substrate (E)-1c.
[7]
In contrast to the (E)-isomer of the α-keto t-butyl ester of o-
tolylhydrazone (E)-1c, the enantioselective alkylation of the
corresponding (Z)-isomer, i.e., (Z)-1c is very sluggish. An attempted
benzylation of (Z)-1c under varying reaction conditions furnished
benzylation product 2c, albeit in low yield. We assume that (Z)-1c may
easily form a stable chelate complex with Cs cation. Hence, the
formation of ammonium enolate is difficult due to the slow ion exchange
between the stable Cs+/hydrazone complex and phase-transfer catalyst,
thereby making the enantioselective alkylation of (Z)-1c very sluggish.
For details on the reactivity of Z-isomeric arylhydrazones, Z/E ratios in
the preparation of o-tolylhydrazones and the photo-induced
isomerization of (Z)-isomers into the corresponding (E)-isomers, see
Supporting Information.
Acknowledgements
This work was partially supported by a Grant-in-Aid for Scientific
Research from the JSPS and MEXT (Japan). The authors also
extend their gratitude to the International Scientific Partnership
Program (ISPP) at the King Saud University for financial support
via ISPP#0072.
[8]
L. Su, M. Xu, Synthesis 2016, 48, 2595-2602.
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